Milk and Blood Pharmacokinetics of Tylosin and Tilmicosin following Parenteral Administrations to Cows

Abstract

The aim of this study is to determine the pharmacokinetics of tylosin and tilmicosin in serum and milk in healthy Holstein breed cows (n = 12) and reevaluate the amount of residue in milk. Following the intramuscular administration of tylosin, the maximum concentrations (C max) in serum and milk were found to be 1.30 ± 0.24 and 4.55 ± 0.23 µg/mL, the time required to reach the peak concentration (t max) was found to be 2nd and 4th h, and elimination half-lives (t 1/2β) were found to be 20.46 ± 2.08 and 26.36 ± 5.55 h, respectively. Following the subcutaneous administration of tilmicosin, the C max in serum and milk were found to be 0.86 ± 0.20 and 20.16 ± 1.13 µg/mL, the t max was found to be 1st and 8th h, and the t 1/2β were found to be 29.94 ± 6.65 and 43.02 ± 5.18 h, respectively. AUCmilk/AUCserum and C max-milk/C max-serum rates, which are indicators for determining the rate of drugs that pass into milk, were, respectively, calculated as 5.01 ± 0.72 and 3.61 ± 0.69 for tylosin and 23.91 ± 6.38 and 20.16 ± 1.13 for tilmicosin. In conclusion, it may be stated that milk concentration of tylosin after parenteral administration is higher than expected like tilmicosin and needs more withdrawal period for milk than reported.

Pharmacokinetics and bioavailability of three promising tilmicosin-loaded lipid nanoparticles in comparison with tilmicosin phosphate following oral administrationin broiler chickens

“…and Pasteurella multocida in broiler chickens. Generally, gram-negative Enterobacteriaceae are resistant to TLM (1)(2)(3)(4).…”

Distribution of hydrophilic and lipophilic antibacterial drugs in skim milk, cream, and casein

“…The in vivo study was performed using a crossover design. The amoxicillin and tylosin doses used in the study were determined by considering the doses used in other studies related to amoxicillin (10-25 mg/kg of BW; Atef et al, 1991;Al Wabel, 2008;Avci and Elmas, 2014) and tylosin (10-17.5 mg/kg of BW; Craigmill et al, 1992;Carceles et al, 1995a,b;Escudero et al, 1996;Elsheikh et al, 1999;Fernandez et al, 2007). Each animal was administered a single i.m.…”

“…Amoxicillin and tylosin concentrations in whole and skim milk, cream, and casein were determined using a HPLC system (Shimadzu, Tokyo, Japan) consisting of a pump (LC-20AT with CBM-20A system controller), a degasser (DGU-14A) to pump the mobile phase, an autosampler (SIL 20A), and a column oven (CTO 10A). The HPLC procedures for amoxicillin and tylosin were based on the methods reported by Karageorgou and Samanidou (2011) and Avci and Elmas (2014), respectively.…”

“…Twenty-five to 47% of tylosin binds to plasma protein and passes readily into milk. Its concentration may be 5 times higher in milk than in plasma (Avci and Elmas, 2014). The withdrawal time for milk is 4 d (8 milkings) after parenteral administration, and the MRL established for tylosin in cow milk is 50 μg/kg (European Union, 2010).…”

“…Although many studies have determined the presence of amoxicillin and tylosin residues in milk, there are no data on the distribution of amoxicillin and tylosin in milk fractions (Luo et al, 1997;Dudriková et al, 1999;Khaskheli et al, 2008;Wang et al, 2008;Martínez-Huelamo et al, 2009;Avci and Elmas, 2014;Li et al, 2014). The aims of this study were (1) to determine the distribution of amoxicillin and tylosin in cream, skim milk, and casein and whether the withdrawal time for different fractions of milk differs according to the physicochemical properties of the drugs; and (2) to determine whether the in vitro assay accurately reflects the distribution of drugs in the different fractions of milk in vivo.…”